There is mounting concern about the oral health consequences of the recent resurgence of smokeless tobacco use among teenage boys in the United States. While the evidence is strongest that smokeless tobacco causes cancer of the oral cavity, there is also evidence that the use of smokeless tobacco increases the risk of cancer of the pharynx, larynx, and oesophagus. Smokeless tobacco also causes a variety of noncancerous and precancerous oral conditions, the most important of which is oral leukoplakia (other less serious oral conditions associated with the use of smokeless tobacco include gum recession and tooth loss). The purpose of this study is to re-examine these relationships using recent large national data sets and examine the possible physiologic mechanisms through which smokeless tobacco acts on oral tissue.